Arterial Occlusive Disease | Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation | springermedicine.com

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BMC Complementary Medicine and Therapies

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Open Access 01-12-2023 | Arterial Occlusive Disease | Research

Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation

Authors: Lei Zhang, Zhihui Yang, Xinyi Li, Yunqing Hua, Guanwei Fan, Feng He

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

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Abstract

Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1β /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1β could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1β were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9.

Practical Applications

Artemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD).

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1.

Zhu K-F, Wang Y-M, Zhu J-Z, et al. National prevalence of coronary Heart Disease and its relationship with human development index: a systematic review. Eur J Prev Cardiol. 2016;23(5):530–43.CrossRefPubMed

2.

Valtorta NK, Kanaan M, Gilbody S, et al. Loneliness and social isolation as risk factors for coronary Heart Disease and Stroke: systematic review and meta-analysis of longitudinal observational studies. Heart. 2016;102(13):1009–16.CrossRefPubMed

3.

Wang C-Y, Liu P-Y, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008;14(1):37–44.CrossRefPubMedPubMedCentral

4.

Schmitz G, Langmann T. Pharmacogenomics of cholesterol-lowering therapy. Vascul Pharmacol. 2006;44(2):75–89.CrossRefPubMed

5.

Zhang LB, Lv JL, Chen HL, et al. Chemical constituents from Artemisia argyi and their chemotaxonomic significance. Biochem Syst Ecol. 2013;50(10):455–8.CrossRef

6.

Adams M, Efferth T, Bauer R. Activity-guided isolation of Scopoletin and Isoscopoletin, the inhibitory active principles towards CCRF-CEM Leukaemia cells and Multi-drug Resistant CEM/ADR5000 cells, from Artemisia Argyi. Planta Med. 2006;72(9).

7.

Hansson GK. Inflammation, Atherosclerosis, and coronary artery Disease. N Engl J Med. 2005;352(16):1685–95.CrossRefPubMed

8.

Huang S, Zhang Z, Li W, et al. Network Pharmacology-Based Prediction and Verification of the active ingredients and potential targets of Zuojinwan for treating Colorectal Cancer. Drug Des Devel Ther. 2020;14:2725–40.CrossRefPubMedPubMedCentral

9.

Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4(11):682–90.CrossRefPubMed

10.

Zuo H, Zhang Q, Su S, et al. A network pharmacology-based approach to analyse potential targets of traditional herbal formulas: an example of Yu Ping Feng decoction. Sci Rep. 2018;8(1):11418.CrossRefPubMedPubMedCentral

11.

Guo P, Cai C, Wu X, et al. An insight into the molecular mechanism of Berberine towards multiple Cancer types through systems Pharmacology. Front Pharmacol. 2019;10:857–7.CrossRefPubMedPubMedCentral

12.

Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6(1):13.CrossRefPubMedPubMedCentral

13.

Xu HY, Zhang YQ, Liu ZM, et al. ETCM: an encyclopaedia of traditional Chinese medicine. Nucleic Acids Res. 2019;47(D1):D976–d982.CrossRefPubMed

14.

Chen ML, Shah V, Patnaik R, et al. Bioavailability and bioequivalence: an FDA regulatory overview. Pharm Res. 2001;18(12):1645–50.CrossRefPubMed

15.

Kim SK, Lee S, Lee MK, et al. A systems pharmacology approach to investigate the mechanism of oryeong-san formula for the treatment of Hypertension. J Ethnopharmacol. 2019;244:112129.CrossRefPubMed

16.

Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–d1082.CrossRefPubMed

17.

Keiser MJ, Roth BL, Armbruster BN, et al. Relating protein pharmacology by ligand chemistry. Nat Biotechnol. 2007;25(2):197–206.CrossRefPubMed

18.

Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51(D1):D638–d646.CrossRefPubMed

19.

Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.CrossRefPubMedPubMedCentral

20.

Wang J, Duncan D, Shi Z et al. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013;41(Web Server issue):W77–83.

21.

Liang B, Xiang Y, Zhang X, et al. Systematic pharmacology and GEO database mining revealed the therapeutic mechanism of Xuefu Zhuyu Decoration for Atherosclerosis Cardiovascular Disease. Front Cardiovasc Med. 2020;7:592201.CrossRefPubMedPubMedCentral

22.

Liu J, Liu J, Tong X, et al. Network Pharmacology Prediction and Molecular Docking-based strategy to Discover the potential pharmacological mechanism of Huai Hua San Against Ulcerative Colitis. Drug Des Devel Ther. 2021;15:3255–76.CrossRefPubMedPubMedCentral

23.

Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with Myocardial Infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937–52.CrossRefPubMed

24.

Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015;15(2):104–16.CrossRefPubMedPubMedCentral

25.

Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic Disease. N Engl J Med. 2017;377(12):1119–31.CrossRefPubMed

26.

Haniff HS, Knerr L, Liu X, et al. Design of a small molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold-small molecule interactions. Nat Chem. 2020;12(10):952–61.CrossRefPubMedPubMedCentral

27.

Vassiliadis E, Barascuk N, Didangelos A, et al. Novel cardiac-specific biomarkers and the cardiovascular continuum. Biomark Insights. 2012;7:45–57.CrossRefPubMedPubMedCentral

28.

Lin M, Jackson P, Tester AM, et al. Matrix metalloproteinase-8 facilitates neutrophil migration through the corneal stromal matrix by collagen degradation and production of the chemotactic peptide Pro-gly-pro. Am J Pathol. 2008;173(1):144–53.CrossRefPubMedPubMedCentral

29.

Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8–27.CrossRefPubMedPubMedCentral

30.

Ridker, P.M., Macfadyen J.G., Thuren T., et al., Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. The Lancet. 2017;390(10105):1833–1842.

31.

Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167.CrossRefPubMedPubMedCentral

32.

Geovanini GR, Libby P. Atherosclerosis and inflammation: overview and updates. Clin Sci (Lond). 2018;132(12):1243–52.CrossRefPubMed

33.

Loke WM, Proudfoot JM, Hodgson JM, et al. Specific dietary polyphenols attenuate Atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscler Thromb Vasc Biol. 2010;30(4):749–57.CrossRefPubMed

34.

Mulvihill EE, Assini JM, Sutherland BG, et al. Naringenin decreases progression of Atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol. 2010;30(4):742–8.CrossRefPubMed

35.

Zeng W, Jin L, Zhang F, et al. Naringenin as a potential immunomodulator in therapeutics. Pharmacol Res. 2018;135:122–6.CrossRefPubMed

36.

Orhan IE, Nabavi SF, Daglia M, et al. Naringenin and Atherosclerosis: a review of literature. Curr Pharm Biotechnol. 2015;16(3):245–51.CrossRefPubMed

37.

Mayerl C, Lukasser M, Sedivy R, et al. Atherosclerosis research from past to present—on the track of two pathologists with opposing views, Carl Von Rokitansky and Rudolf Virchow. Virchows Arch. 2006;449(1):96–103.CrossRefPubMed

38.

Grebe A, Hoss F, Latz E. NLRP3 inflammasome and the IL-1 pathway in Atherosclerosis. Circ Res. 2018;122(12):1722–40.CrossRefPubMed

39.

Kanehisa M, Furumichi M, Sato Y, et al. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2022;51(D1):D587–92.CrossRefPubMedCentral

Title: Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
Authors: Lei Zhang
Zhihui Yang
Xinyi Li
Yunqing Hua
Guanwei Fan
Feng He
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Arterial Occlusive Disease
Published in: BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-023-04223-1

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